Traditionally, the brain was considered as an immune-privileged organ. However, the re-discoveries of meningeal lymphatic vessels have revolutionized our understanding, revealing direct physical and functional connections between the central nervous system and the peripheral immunity. Meningeal lymphatic vessels play a crucial role in draining cerebro-spinal fluid, clearing metabolic waste from the brain, eliciting immune surveillance and maintaining immune homeostasis within the brain. They are implicated in the pathogenesis and progression of multiple central nervous system diseases. This review mainly focuses on the anatomical structure and physiological functions of meningeal lymphatic vessels, with brief introduction to their role in neurological diseases. We summarize recent research advances in meningeal lymphatic vessels, and provide insights for further research and clinical applications.

Oligodendrocytes are myelin-forming cells of the central nervous system (CNS). The processes extending from each oligodendrocyte are capable of wrapping axon to form multiple myelin sheaths to ensure efficient and rapid conduction of action potentials along the axon. Recent studies have shown that myelin changes are quite active although most of the myelin sheaths in the adult brain are in a stable state. On the one hand, oligodendrocyte precursor cells continue to differentiate to form new myelin sheaths; on the other hand, a small portion of the formed myelin sheaths degenerate over time. Dynamic changes in myelin sheaths are thought to be a form of neural plasticity in the adult brain, which aims to regulate the function of neural circuits for adapting of new environments or acquiring new skills. In the brains with Alzheimer's disease (AD), myelin degeneration can lead to a compensatory increase in myelin regeneration, but it is still insufficient to compensate for the loss of myelin, and the promotion of new myelin formation is expected to be a new strategy to improve AD-related cognitive dysfunction.

An increasing number of studies have been focused on the field of immune system in the central nervous system（CNS），as the viewpoint of CNS immune privilege being challenged. Among them, CNS boarder-associated macrophages（BAMs）play a prominent role in the regulation of brain homeostasis and related diseases. Unlike microglia located in the brain parenchyma, BAMs are a type of specialized macrophages located in the meninges (including dura, arachnoid, and leptomeninges) ,perivascular spaces, and choroid plexus. They are crucial for immune surveillance, cerebrospinal fluid drainage, antigen clearance, material exchange, and etc. Here, we reviewed a series of relevant studies on the origin and roles of BAMs in CNS, so as to broaden the understanding of the mechanisms of by which BAMs maintain the brain homeostasis, as well as provide novel insights into the treatment of CNS diseases including Alzheimer 's disease.

Objective To study the distribution and effect of growth hormone receptor (GHR) positive neurons in neonatal mouse brain Methods Six GHR-CreERT;mTOMATO/mGFP fluorescent reporter gene mice were selected. All of them were induced with tamoxifen on the 3rd day after birth. On the 10th and 17th days, 3 mice were sampled respectively at each time point. The distribution of GHR-positive neurons in the developing brain was observed at different stages. GHR floxed mice were generated. By crossing them with neuron-specific Thy1-CreERT;YFP mice, GHR was induced to be knocked out in neurons. Control mice (GHR fl/fl, 4 mice) and conditional knockout mice (Thy1-CreERT;YFP;GHR fl/fl, 4 mice) were induced on the 3rd day after birth. Samples were collected on the 10th day for observing the effect of neuronal GHR signaling on brain development. Results The GHR fluorescent reporter gene mice showed that GHR-positive cells are widely expressed in the developing mouse brain. GHR-positive neurons are concentrated in the paraventricular hypothalamic nucleus (PVN). After specifically knocking out GHR in neurons of the developing mouse brain, no significant differences were observed in the areal densities of neurons and various types of glial cells. Conclusion GHR-positive neurons are mainly concentrated in the PVN. Knocking out GHR in neurons of the developing brain cannot significantly change the morphology and density of various neural cell types.

 Objective To explore the morphological features of the neural projection pathway from the dorsal raphe nucleus (DRN) to the claustrum (CLA) in mice.  Methods After injection of the retrograde tracer 594 retrobeads into the right CLA (n=3) or the anterograde tracer biotinylated dextran amine(BDA) into the DRN (n=3),  the distribution and the neurochemical feature of the retrogradely labeled neurons in the DRN, as well as the locations of nerve fibers and terminals throughout the brain and within the CLA, were observed by a combined immunofluorescent staining for 5-hydrozytryptamine(5-HT). The downstream target of the DRN-CLA projection was studied by injection of rabies retrograde monosynaptic virus (RV) into calcium ion/calmodulin dependent protein kinaeⅡ(CaMKⅡ)-Cre or glutamate decarboxylase 67(GAD67)-Cre mice. Results Retrograde labeled neurons were observed in the rostral, middle, and caudal segments of the DRN, with those in the middle segment and in the ventral part of the nucleus (DRV) the densest. Over 90% of the retrograde labeled neurons were 5-HT positive. After injection of BDA into the DRN, dense fiber projections were observed in the ventral tegmental area, parafascicular nucleus, ventral pallidum, and central amygdala nucleus. In comparison, DRN derived fibers and terminals in the CLA were relatively sparse. After injection of RV trans-synaptic virus into the CLA of CaMKⅡ-Cre and GAD67-Cre mice, respectively, dense RV-labeled presynaptic neurons were observed in the DRN of CaMKⅡ-Cre mice, while those in the DRN of GAD67-Cre mice were rather sparse.Conclusion The DRN-CLA projection pathway is characterized by the dense 5-HTergic neurons in the DRV, the relatively sparse fibers or terminals in the CLA, and a primary synaptic connection with CaMKⅡ positive neurons in the CLA. 

Objective To analyze the molecular markers of various nuclei in the human basal ganglia and the differentially expressed genes (DEGs) among different nuclei, gender, and Parkinson’s disease (PD), followed by the biological function annotations of the DEGs. Methods Forty-five specimens of basal ganglia from 10 human postmortem brains were divided into control and PD groups, and the control group was further categorized into female and male groups. RNA from each sample was extracted for high-throughput transcriptome sequencing. Bioinformatic analysis was conducted to identify molecular markers of each nuclei in the control group, nuclei-specific, gender-specific, and PD-specific DEGs, followed by gene enrichment analysis and functional annotation. Results Sequencing analysis revealed top DEGs such as DRD1, FOXG1, and FAM183A in the caudate; SLC6A3, EN1, SLC18A2, and TH in the substantia nigra; MEPE and FGF10 in the globus pallidus; and SLC17A6, PMCH, and SHOX2 in the subthalamic nucleus. In them, putamen showed some overlapping DEGs with caudate, such as DRD1 and FOXG1. A significant number of DEGs were identified among different nuclei in the control group, with the highest number between caudate and globus pallidus (9321), followed by putamen and globus pallidus (6341), caudate and substantia nigra (6054), and substantia nigra and subthalamic nucleus (44). Gene enrichment analysis showed that downregulated DEGs between caudate and globus pallidus were significantly enriched in processes like myelination of neurons and cell migration. Upregulated DEGs between putamen and globus pallidus were enriched processes like chemical synaptic transmission and regulation of membrane potential, while downregulated DEGs were enriched in myelination and cell adhesion. Upregulated DEGs between caudate and substantia nigra were enriched in processes like chemical synaptic transmission and axonal conduction, while downregulated DEGs were enriched in myelination of neurons. Totally 468, 548, 1402, 333, and 341 gender-specific upregulated DEGs and 756, 988, 2532, 444, and 1372 downregulated DEGs were identified in caudate, putamen, substantia nigra, globus pallidus, and subthalamus nucleus. Gene enrichment analysis revealed upregulated DEGs mostly enriched in pathways related to immune response and downregulated DEGs in chemical synaptic transmission. At last, 709, 852, 276, 507, and 416 PD-specific upregulated DEGs and 830, 2014, 1218, 836, and 1730 downregulated DEGs were identified in caudate, putamen, substantia nigra, globus pallidus, and subthalamus nucleus. Gene enrichment analysis revealed upregulated DEGs mostly enriched in apoptotic regulation and downregulated DEGs in chemical synaptic transmission and action potential regulation. Conclusion We identified and analysed the molecular markers of different human basal ganglia nuclei, as well as DEGs among different nuclei, different gender, and between control and PD.

With the improvement of China’s socioeconomic status, the issue of aging has become increasingly prominent, making cerebral infarction a common disease among the elderly. In recent years, research on cerebral infarction has gradually deepened, shifting focus from merely protecting and repairing neurons to emphasizing the complex interplay between inflammatory response and autophagy in the brain vascular unit, covering various aspects such as the blood-brain barrier, astrocytes, microglia, and autophagy. This shift in research direction has provided us with a profound understanding of the mechanisms underlying cerebral infarction, offering strong support for innovative future treatment strategies. In this review, we delved into the importance of the interplay between inflammatory response and autophagy in the pathogenesis of cerebral infarction, emphasized the intricate interactions among these biological components, which might lay the groundwork for more effective managements and treatments of cerebral infarction. By comprehensively reviewing existing literatures, we proposed future research directions, aiming to provide more scientific and systematic guidance for the clinical management and treatment of cerebral infarction. 

Objective   To study the effects of 7week treadmill exercise combined with black lycium polysaccharide on depression-like behaviors and explore the alterations of hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor （AMPAR）associated pathways in mice.  Methods   Fifty male Kunming (KM) mice were randomly divided into blank group (K, n=10) and chronic unpredictable mild stress group（CUMS, n=40）. For the CUMS group, 13 random chronic unpredictable mild stress method  were used to induce depression-like behaviors. After successful modeling, the mice were further divided into model group (M), treadmill exercise group (E), black lycium polysaccharide group (L), and treadmill exercise combined with black lycium polysaccharide group (EL); each group contained 10 mice, and intervention lasted for 7 weeks. The behavioral assessment was performed; the contents of 5-hydroxytryptamine（5-HT）, brain-derived neurotrophic factor (BDNF) and dopamine (DA) in hippocampal tissue, and the levels of S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE）in serum were detected; Nissl staining was carried out to observe the structure of brain tissue; AMPAR, glutamate receptor 1(GluR1) and calcium/calmodulin-dependent protein kinase α (CaMKⅡα) proteins in hippocampal tissue were detected; Real-time PCR was used to verify the expression of hippocampal AMPAR, GluR1 and CaMKⅡα mRNA obtained by mRNA sequencing.  Results   1. Compared with the blank group, the mice in CUMS group had obvious depression-like behaviors (P<0.01); the contents of 5-HT, BDNF and DA in hippocampal tissue decreased significantly, while those of S100B and NSE increased (P<0.01); Neurons in the prefrontal cortex were absent, the Nissl nacleus was condensed, and the arrangement was irregular and sparse. 2. Compared with the model group, the behavioral assessment of the mice in the E, L and EL groups were significantly improved, reflecting that the contents of 5-HT, BDNF and DA in hippocampal tissue increased, and the serous S100B and NSE levels decreased (P<0.01 or P<0.05); for sucrose preference test (SPT) and forced swimming test (FST), S100B and NSE content result  showed that treadmill exercise and black lycium polysaccharide intervention had a synergistic effect on behavioral improvement. 3. Compared with the model group, the contents of AMPAR, GluR1, and CaMKⅡα proteins in hippocampal tissue of mice in the E, L and EL groups increased (P<0.01), and there was a synergistic effect between treadmill exercise and black lycium polysaccharides; the Illumina high-throughput sequencing data showed that there were 49 upregulated genes and 18 down-regulated genes involving learning and memory, and neuronal damage repair, etc. which were closely related to postsynaptic membrane location of AMPA receptors and synaptic long-term potentiation and long-term depression, The increased transcriptions of AMPAR, GluR1 and CaMKⅡα revealed by the sequencing were verified by Real-time PCR data, and there was a synergistic effect between the treatments of treadmill exercise and black lycium polysaccharides.  Conclusion   Seven weeks of treadmill exercise and administration of black lycium polysaccharides can improve depression-like behaviors in mice, possibly by affecting the phosphorylation of CaMKⅡα to regulate AMPAR activity, promote neuronal damage repair and improve synaptic plasticity and function.

Objective  To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research. Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed (from December 2019 to February 2024), including gender, age, cause of death, as well as quality control data such as postmortem delay time, pH value of cerebrospinal fluid and and RNA integrity number and result  of neuropathological diagnosis. Results  Until February 2024, 30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University, with a male to female ratio of 9∶1. Donors over 80 years old accounted for 53%. Cardiovascular and cerebrovascular diseases (36.67%) and nervous system diseases (23.33%) accounted for a high proportion of the death causes. The location of brain tissue donors in Shijiazhuang accounted for 90% donations, and the others were from outside the city. The postmortem delay time was relatively short, 90% within 12 hours and 10 % more than 12 hours. 69.23% of the brain samples had RNA integrity values greater than 6. Cerebrospinal fluid pH values ranged from 5.8 to 7.5, with an average value of 6.60 ± 0.45. Brain weights ranged from 906-1496g, with an average value of（1210.78 ± 197.84）g. Three apolipoprotein E (APOE) alleles were detected including five genotypes (ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, ε4/ε4). Eleven staining methods related to neuropathological diagnosis had been established and used. A total of 12 cases were diagnosed as neurodegenerative diseases (including Alzheimer’s disease, Parkinson’s disease, multiple system atrophy, corticobasal degeneration and progressive supranuclear palsy，etc.), accounting for 40% donated brains. The comorbidity rate of samples over 80 years old was 100%.  Conclusion  The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province, and it can also be more targeted to understand and identify potential donors. Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research. 

Objective  To explore the differences in the robustness of structural covariance networks among populations with different circadian rhythm preferences, and to constructing brain structural covariance networks based on gray matter volume and cortical thickness. Methods  Morphological metrics of gray matter from early chronotype and late chronotype volunteers was extracted by using the CAT12 toolbox. Structural covariance networks based on gray matter volume and cortical thickness were constructed according to the LPBA40 atlas and Desikan-Killiany atlas. Graph theoretical parameters were calculated and the resilience of structural covariance networks against deliberate attacks were assessed by utilizing the GAT toolbox to observe the network’s robustness. Results  In the structural covariance network constructed based on gray matter volume, when using betweenness centrality as the target of deliberate attacks and network size as the measure of network robustness, the structural covariance network of early chronotype volunteers exhibits greater robustness than that of late chronotype volunteers (P<0.05).When using node degree as the target of deliberate attacks and network size as the evaluation metric for network robustness, the structural covariance network robustness of early chronotype volunteers showed no statistically significant difference compared with the late chronotype volunteers (P>0.05).In the structural covariance network constructed based on cortical thickness, when using betweenness centrality or node degree as the targets of deliberate attacks, and network size as the evaluation metric for network robustness, the structural covariance network robustness of early chronotype volunteers was weaker than that of late chronotype volunteers (P<0.05). Conclusion  The covariance relationships among brain gray matter morphology vary among populations with different circadian rhythm preferences, and the differences in structural covariance network robustness may be one of the manifestations, which provides a new understanding of the neuroanatomical features related to circadian rhythm.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system(CNS), which is characterized by infiltration of immune cells, glia activation, demyelination and neurodegeneration. With the progression of MS, the peripheric infiltrated immune cells promote lymphocytes to locate in parenchyma or meninges adjacent to active lesions by secreting cytokines, such as C-X-C motif chemokine ligand (CXCL)13, CXCL12 and tumor necrosis factor-α(TNF-α), contributing to the formation of tertiary lymphoid structure (TLS). TLS formation in the CNS can directly trigger immune reaction independent from peripheral immune system, leading to the differentiation of pathogenic lymphocytes, the activation of microglia and astrocyte, and the recruitment of additional peripheral immune cells into the CNS by secreting proinflammatory cytokines and chemokines. The immune reaction in CNS caused by TLS leads to aggravated neuroinflammation and pathological changes, even irreversible neuron damage, which is thought to be responsible the progression of MS. The formation, distribution, tissue structure, and the mechanism of formation and distribution of the TLS in MS are reviewed in this article, which may contribute to potential therapeutic approaches for chronic progressive MS. 

Objective To analyze the cerebral blood flow changes in patients with newly diagnosed untreated early-onset depression (EOD), using three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL), and to explore its relationship with clinical phenotypes. Methods The Hamilton Depression Scale (HAMD), Childhood Trauma Questionnaire (CTQ) scores, 3D T1WI, and 3D-pCASL brain images of 65 untreated EOD patients and 55 healthy volunteers(HC group) were collected. SPM 12 and DPABI_V7.0 software were used to preprocess and analyze the whole brain images in two groups. Xjview software was used to analyze the value of cerebral blood flow (CBF) at the whole brain level of the two groups, and SPSS 25.0 software was used to evaluate the correlation of CBF values with HAMD scores and CTQ scores. Results Compared with the HC group, the CBF of the EOD group was reduced significantly［P<0.05,  cluster size>50, false discovery rate(FDR) correction］ in the right opercular inferior frontal gyrus (t=5.89), right temporo-parieto-occipital (TPO) region (t=6.49), and blood perfusion increased significantly (P<0.05, cluster size>50, FDR correction) in the left superior frontal gyrus (t=5.31) and left insular lobe (t=4.70). Conclusion The proportion of EOD patients with childhood trauma experience is relatively large. EOD patients have both reduced areas and increased areas in cerebral perfusion. The CBF value of the right TPO area is negatively correlated with HAMD scores; The CBF value of the left superior frontal gyrus is positively correlated with the total score of CTQ and the index of physical neglect score in CTQ, which is different from the result  of studies that do not distinguish between early-onset and late-onset depression. 

 

Objective  To investigate the effects of leptin on hypothalamic neuron activity and lipid metabolism in adipose tissue of obese mice. Methods 10 leptin-deficient obese (ob/ob) mice with homozygous mutation of leptin gene and 10 wild-type（WT）mice born in the same litter were randomly divided into control group and leptin treatment group. The activity of pro-opiomelanocortin(POMC) neurons and tyrosine hydroxylase(TH⁺) neurons, the morphological changes of adipose tissue and the expression of lipid-related genes were analyzed by immunofluorescent staining, HE staining and Real-time PCR. Results  Compared with the WT mice, the ob/ob mice showed decreased activity of POMC neurons and TH⁺ neurons and larger cell diameter in adipose tissue and liver tissue. In addition, the expressions of heat-related genes uncoupling protein 1(UCP1), cytochrome c oxidase subunit 8B(Cox8b) and cell death-inducing DNA fragmentation factor, alpha subunit-like effector A(Cidea) in subcutaneous white fat in ob/ob mice decreased significantly, and the expressions of lipid synthesis-related genes sterol regulatory element binding transcription factor 1(Srebp1) and fatty acid synthase(Fas) increased significantly. After treated with leptin, the activities of POMC and TH⁺ neurons were increased, and the cellular diameter and the degree of vacuolar degeneration were reduced in the adipose tissue and liver. Further analyses showed that the expressions of thermogenesis-related genes and lipolysis-related genes were increased, but expressions of lipid synthesis-related genes were reduced in brown adipose tissue. Conclusion  Leptin treatment could prevent the increasing of obesity in ob/ob mice, which is associated with increased lipolysis and reduced lipid synthesis through activation of hypothalamic POMC neurons and peripheral adipose tissue sympathetic nervous system

Objective  To explore the neuronal properties of the pathway from the medial prefrontal cortex (mPFC) to the paraventricular thalamic nucleus of (PVT) and to investigate the effect of modulation of the pathway on physiological pain and acute pain in mice. Methods  CTb was injected into the PVT of GAD67-GFP transgenic mice, and the properties of mPFC neurons projected to PVT were observed. The mPFC-PVT pathway was activated or inhibited by chemogenetics to observe the effects on physiological pain, such as mechanical pain, thermal pain, cold pain, and on capsaicin induced inflammatory pain. Results  CTB-labeled neurons in the mPFC were mainly distributed in layer V and layer VI, and were not double-labeled with GAD67-GFP. Chemogenetic activation of the mPFC-PVT pathway significantly decreased the mechanical pain threshold (p < 0.0001) and shortened the thermal pain latency (p < 0.001), but had no obvious effects on cold pain. Inhibition of this pathway significantly increased the mechanical pain threshold (p < 0.05). Activation of the pathway increased the paw licking time (p < 0.05) in acute inflammatory pain induced by intraplantar injection of capsaicin. Conclusion  mPFC-PVT pathway is a non GABAergic projection and its activation can promote mechanical pain, thermal pain, and acute inflammatory pain in mice.

Objective To explore the mechanism of ceruloplasmin(CP) in brain iron metabolism. Methods  We obtained glial fibrillary acidic protein(GFAP)-cre-mediated ceruloplasmin knockout mice (CP^GFAP cKO mice) by crossing CP^flox/flox mice with transgenic GFAP-cre mice. Eighty-eight male mice aged 6 months were divided into four groups, WT, GFAP-cre, CP^flox/flox and CP^GFAP cKO. To observe whether astrocytic CP gene knockout specifically through genotype identification and immunofluorescent staining, and Western blotting method. The learning and memory function was detected by Morris water maze, brain iron levels in the cortex and hippocampus of mice were measured by inductively coupled plas mamass spectrometry(ICP-MS) and μ-probe X-ray fluorescence(μ-XRF), and iron contents in serum and liver were detected by iron kit. Results The mice of conditional knockout ceruloplasmin in astrocytes were obtained successfully by genotype identification, immunofluorescent staining and Western blotting method. The learning and memory ability was reduced in the water maze experiment, and iron contents decreased in the cortex and hippocampal regions of 6-month-old CP^GFAP cKO group. While the level of serum iron and liver iron in the four groups did not change significantly. Conclusion The decline of learning and memory ability of mice with astrocytic CP gene knockout specifically is closely related to the decrease in brain iron. The main function of CP may be to help brain cells to absorb iron.

Objective To calculate the diffusion tensor image analysis along the perivascular space(DTI-ALPS) index, evaluate the function of the glymphatic system, observe the changes in the DTI-ALPS index during the aging process, and find the relationship between the DTI-ALPS index and correlates of certain executive functions that reflect mental flexibility, based on DTI-ALPS. Methods The FSL toolbox was used to extract the DTI-ALPS index of the dominant hemisphere of the brain of adult subjects in the NKI Rockland Sample data set, and the correlations between the DTI-ALPS index and age and design fluency practical accuracy were analyzed, respectively. Differences in DTI-ALPS index among different age groups and the mediating effect of DTI-ALPS index between age and design fluency practical accuracy were analyzed. Results The DTI-ALPS index was negatively correlated with age (r=-0.288, P<0.001), but there was a local peak of recovery in the 60-69 age group (P<0.01).The DTI-ALPS index was positively correlated with the design fluency practical accuracy (r=0.258, P=0.001).The mediating effect of DTI-ALPS index between age and design fluency practical accuracy was statistically significant (P<0.05), and the mediating effect accounted for 22.1% of the total effect. Conclusion  The DTI-ALPS index showed an overall downward trend during the aging process, but there is a local peak of recovery in the 60-69 age group. At the same time, the DTI-ALPS index might be related to certain executive functions that could reflect thinking flexibility. 

Objective   To investigate the effect of microplastic (MPs) exposure on learning and memory in mice, and its mechanism by observing the protein expression of brain-derived neurotrophic factor (BDNF) /tyrosine receptor kinase B (TrkB) /N-methyl-D-aspartate receptor subtype 2B (NR2B) signaling pathway and neurogenesis.  Methods  Forty male C57BL/6 mice were randomly divided into control group (Ctrl) and microplastics exposure group (MPs). Mice in MPs group were treated with 0.3 mg/(kg·d) microplastics, administered by gavage at a volume of 200 μl for 30 consecutive days. Morris water maze test was used to evaluate the spatial learning and memory ability of mice. Western blotting was used to detect the protein levels of BDNF, TrkB and NR2B in hippocampus of mice. Immunofluorescent staining was used to observe the number of doublecortin (DCX) and neuronal nuclei antigen (NeuN) positive cells in the hippocampus of mice to evaluate hippocampal neurogenesis.  Results  Compared with the control group, the ability of learning and memory decreased significantly in MPs group mice (P<0.01). The expression levels of BDNF, TrkB and NR2B in the hippocampus of MPs group mice were significantly lower than those of control group (P<0.05). The number of DCX and NeuN positive cells in the hippocampus of MPs group was significantly lower than that of control group (P<0.01).  Conclusion   MPs exposure induces learning and memory impairment which may be related to inhibiting BDNF/TrkB/NR2B signaling pathway and reducing hippocampal neurogenesis. 

Objective To observe the effect of hyolroxylsafflor(HSYA) on cyclooxygenase-2(COX-2)/ prostaglandin E₂(PGE₂) signaling pathway, and to investigate the protective effect and mechanism of HSYA on cerebral ischemia-reperfusion injury（CIRI）. Methods Totally 90 SD male rats were randomly divided into sham-operated group(S group), operation group(CIRI group), HSYA group and celecoxib group(C group), HSYA group subdivided into HSYA low dose group(HSYA-L group), HSYA medium dose group (HSYA-M group)and HSYA high dose group(HSYA-H group), 15 rats in each group. CIRI model was prepared by thread embolism method. The rats in each group were given intraperitoneal injection 30 minutes before operation. HSYA groups were given HSYA 10 mg/kg, 15 mg/kg, 25 mg/kg respectirely; C group was given celecoxib 40 mg/kg; S group and CIRI group were given the same amount of normal saline. Neurofunctional scores of each group of rats were performed immediately after recovery from modeling, cerebral infarction volume was measured 24 hours after reperfusion; At the same time, neuronal injury was observed by Nissl staining, the changes of COX-2 mRNA and protein were detected by Real-time PCR and Western blotting, and the changes of PGE₂, tumor necrosis factor α(TNF-α) and interleukin(IL)-1β were detected by ELISA.   Results  Compared with the S group, in the CIRI group, neurofunctional scores increased dramatically (P<0.05), the volume of cerebral infarction increased dramatically (P<0.05), the damage of neurons increased and the number of neurons decreased dramatically (P<0.05), the expressions of COX-2 mRNA and protein increased dramatically (P<0.05), meanwhile the expressions of PGE₂, TNF-α and IL-1β were also found dramatically increased (P<0.05); Compared with the CIRI group, in the HSYA group and C group, neurofunctional scores decreased dramatically (P<0.05), the volume of cerebral infarction was reduced dramatically (P<0.05), the damage of neurons decreased and the number of neurons increased dramatically (P<0.05), the expressions of COX-2 mRNA and protein, PGE₂, TNF-α and IL-1β decreased dramatically(P<0.05). The differences between HSYA groups and both HSYA-L group and HSYA-M group compared with the C group were obvious(P<0.05), while no obvious differences were found in HSYA-H group compared with the C group(P>0.05). Conclusion  HSYA alleviates reperfusion injury in ischemic stroke may be related to the inhibition of COX-2/PGE₂ signaling pathway. 

Objective   To explore the mechanism of Angelica Sinensis polysaccharide (ASP) promoting donor bone marrow transplantation (BMT) to reconstruct hematopoietic function of receptor mice by regulating bone marrow stromalcells (BMSCs).  Methods   Bone marrow mononuclear cells (BMMNCs) of male C57BL/6J mice aged 8-10 weeks were separated, purified and transplanted into female receptor mice of the same age. On the ninth day, receptor mice BMMNCs were separated, purified and transplanted again into female receptor mice. The transplanted receptor mice were divided into control group:  sham irradiation; Irradiation(IR) group: a whole-body irradiation with a total dose of 8.0 Gy X-ray; BMT group: the receptor mice treated in the same way as the IR group and transplanted BMMNCs (5×106 cells) from male donor via the tail vein; BMT+ASP group: the receptor mice treated in the same way as the BMT group, and injected ASP ［100 mg/（kg·d）×9］ by intraperitoneal route from the first day of transplantation. Changes in body weight and survival rate of mice were recorded during modeling, receptor mice BMMNCs were collected to detect sexdetermining region of Y(SRY) gene after building model, peripheral blood indexes, the number of BMMNCs in femur and histopathology of bone marrow were detected; BMSCs in receptor mice was separated and purified, BMSCs adhesion ability was observed, proliferation ability was detected by 5-ethynyl-2-deoxyuridine(EdU);The level of reactive oxygen species (ROS), the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in BMSCs were detected; The levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), stem cell factor(SCF), insulinlike growth factor 1(IGF-1) in culture supernatant of BMSCs were determined, CFU-Mix was counted after BMMNCs co-cultured with receptor BMSCs in each group for 48 hours;The expression of Notch signaling pathway related genes (Notch1, Jagged1, Hes1) in BMMNCs were measured by Real-time PCR.    Results   All mice in IR group were died,the body weight loss in BMT+ASP group was not obvious. The SRY gene was detected in the receptor female mice BMMNCs. Peripheral blood indexes and the number of BMMNCs were not significantly decreased in BMT+ASP group receptor mice,and bone marrow histopathological injury was reduced. ASP promoted the proliferation of BMSCs, decreased the contents of ROS and MDA, and increased the activity of SOD in BMSCs. ASP promoted the secretion of SCF, GM-CSF and IGF-1 in BMSCs, and increased CFU-Mix yield of BMMNCs co-cultured with receptor BMSCs. ASP increased the expression of Notch1, Jagged1 and Hes1 mRNA in BMMNCs.  Conclusion   The mechanism of ASP promoting receptor hematopoietic function reconstruction is related to reducing the oxidative stress damage of hematopoietic microenvironment, improving the secretion of hematopoietic growth factors in BMSCs, and regulating Notch signaling pathway. 

Epilepsy is a common chronic neurological disorder caused by abnormal electrical activity in the brain, and its pathogenesis has not been fully clarified. In recent years, more and more studies have shown that iron, zinc and copper in the brain are involved in the occurrence and development of epilepsy. These metal ions possibly play a role in epileptogenesis by affecting neuronal excitability and signal transduction through alterating ion channel function, potential balance, action potential propagation, redox and so on. In this review, we mainly analyse the effects of these metal ions on epilepsy, in order to explore the underlying mechanisms of epilepsy and provide promising therapeutic strategies for epilepsy based on metal ions. 

Objective  To explore the common features of Chinese ethnic groups.  Methods   Eight body indexes of 62 ethnic groups in China were analyzed.  Results   The cluster analysis showed that 52 males and 59 females ethnic groups were grouped into the mixed group dominated by the northern ethnic group and the mixed group dominated by the southern ethnic group. Eight Han ethnic groups were grouped into each group, but no Han group was aggregated. The result  of body index classification showed that the main body types of Chinese male population were long trunk, middle chest, wide shoulder, wide pelvis and middle leg. Middle body, wide chest, wide shoulder, wide pelvis and middle leg were the main body types of Chinese female population. This showed that the characteristics of Chinese ethnic groups had obvious consistency. The consistency of Chinese group features was related to its close origin. It should be said that Han nationality played an important role in the process of communication and integration of various ethnic groups in China. In the history of the Han nationality, there had been many large-scale population migration. The southern movement of the northern ethnic minorities into the northern Han and the southward movement of the northern Han into the south promoted the formation of the Southern Han, which made the southern Han and the northern Han had similar body features, and also promoted the southern ethnic minorities into the southern Han. In addition, the Han nationality who moved into minority areas also gradually integrated into minority areas. Conclusion   There are obvious commonalities in Chinese ethnic groups. 

Objective To establish an acute exposure model of extreme plateau hypobaric hypoxia environment and explore transcriptomic changes related to learning and memory impairment in rats.  Methods Healthy male SD rats aged 6-weeks, 200-250 g, were selected and divided into control group and plateau group. The control group was treated with normal pressure and oxygen (19 rats), and the plateau group was placed in a hypobaric hypoxia chamber (19 rats) at a simulated altitude of 8000 meters and treated for 72 hours. Behavioral changes were detected with 16 animals from each group using contextual fear conditioning and Morris water maze (8 rats each). Three hippocampal tissues were extracted from each group for transcriptomic sequencing, and the molecular mechanism of learning and memory impairment induced by extreme plateau environment was analyzed by Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG) and gene set enrichment analysis(GSEA) enrichment.  Results The behavioral result  showed that compared with the control group, the fear memory and spatial learning memory abilities of rats in plateau group were decreased. GO and KEGG analyses showed that the extreme altitude environment reshaped the hippocampal microenvironment and affected the intercellular signal transmission, while GSEA analysis showed that the extreme altitude environment up-regulated the gene set related to the plasma membrane and extracellular matrix.  Conclusion The extreme plateau environment at an altitude of 8000 meters could affect the microenvironment of rat hippocampus, destroy intercellular connections and impair intercellular communication and then induce learning and memory impairment. 

 

Objective To investigate whether microRNA(miR)-199a-5p regulates blood-brain barrier(BBB) integrity through PI3K/Akt pathway after cerebral ischemia. Methods  A permanent middle cerebral artery occlusion (MCAO) model was established in SPF adult male SD rats. Totally 48 rats were randomly divided into sham group (n=12), model group(n=12), MCAO+miR-199a-5p group(n=12), and MCAO+miR-199a-5p negative control group(n=12). The Ludmila Bellayev 12 point score was used to evaluate the neurobehavioral performance of rats; The integrity of the BBB after ischemia stroke was detected through Evans blue staining; Immunofluorescent staining was used to determine apoptosis after cerebral ischemia; Western blotting technology was used to detect the protein expression of claudin-5, phosphatidylinositol-3 kinase regulatory subunit 2(PIK3R2), p-Akt, Akt, and vascular endothelial growth factor (VEGF)-A; Real-time PCR was used to investigate the expression levels of miR-199a-5p, claudin-5, and VEGF-A in the ischemic penumbra and infarcted area of the brain.  Results The result  showed that miR-199a-5p mimic intervention improved proprioception and motor ability in MCAO rats. MiR-199a-5p mimic reduced the expression of PIK3R2 following ischemia stroke, activated the Akt signaling pathway, and increased the expression of claudin-5 and VEGF-A in the ischemic penumbra. In addition, miR-199a-5p alleviated inflammation after cerebral ischemia. MiR-199a-5p mimic reduced BBB permeability and reduced neuronal apoptosis after cerebral ischemia. Conclusion MiR-199a-5p can reduce the expression of PIK3R2 following ischemic stroke, activate the Akt signaling pathway, reduce the expression of inflammatory cytokines, and alleviate the damage to the blood-brain barrier. 

Objective  To explore the distribution and localization of dopamine receptor D3-D5 in the small intestine of different species.  Methods   The distribution and expression of D3-D5 in the small intestine of mice, rats and rhesus monkeys were detected by immunohistochemistry and Western blotting. The expression of D3-D5 in immunoglobulin A positive plasma cells (IgA+PC) located in the lamina propria (LP) were detected by immunofluorescence double labeling.  Results   D3 and D5 were widely distributed in the epithelium, LP, submucosal plexus (SMP) and intermuscular plexus (MP) of the small intestine in mice, rats and rhesus monkeys. The distribution of D4 in the small intestinal of mice and rhesus monkeys were consistent with the result  of D3 and D5. D4 was distributed only within the epithelium and LP of rat small intestine. D3 and D5 were expressed in the IgA+PC in the LP of mice and rats, whereas D4 was not.  Conclusion  The distribution and localization pattern of D3 and D5 are similar in the small intestine of mice, rats and rhesus monkeys, whereas those of D4 vary between different species. Dopamine may be involved in regulating the functions of IgA+PC. 

Ovarian cancer is one of the most common gynecologic cancers in the world. Over the past few decades, there has been considerable research reporting on the mechanisms of cancer development and progression, with multiple nerve as well as neurotransmitters involved. Nerve innervation is also found in ovarian cancer. And in ovarian cancer, various nerves and neurotransmitters play different roles. They are involved in ovarian cancer cells’ proliferation metastasis, apoptosis and changes in the tumor microenvironment. Further understanding of the role of these nerve endings in the development of ovarian cancer is essential for understanding the mechanisms of cancer progression. This will be important for subsequent research focusing on tumor regulation. While glucocorticoids and sympathetic nerve-released norepinephrine are able to promote ovarian cancer progression, serotonin may inhibit cancer cell growth. Also, parasympathetic and sensory nerves are capable of having either a positive or negative effect on ovarian tumors. These relevant studies offer the possibility of new therapeutic options for oncology, it may be possible to mitigate the progression of cancer with inexpensive receptor inhibitors or agonists. This will facilitate the subsequent exploration of therapeutic possibilities forovarian cancer and other cancer-related treatments. In this review, we also present some insights into the role of the nervous system in the regulation of ovarian cancer, which we hope will provide new insights into the innervation and progression of ovarian cancer. 

Objective   To observe the effect of electric stimulation on nuclear factor-κB (NF-κB)/ NOD-like receptor protein 3 (NLRP3) signaling pathway and microglial cell morphology in mice with lipopolysaccharide（LPS）induced chronic neuroinflammation, and to explore the protective mechanism of electric stimulation on brain of mice.  Methods   C57BL/6 mice were randomly divided into blank control group (n=8), model group (n=12), sham electroacupuncture group (n=6) and electroacupuncture group (n=6). Except blank control group, mice in other groups were injected intraperitoneally with LPS (0.25mg/kg) for 7 consecutive days. On the 8th day, mice in the sham electroacupuncture group and electroacupuncture group were treated with acupuncture or Zusanli electroacupuncture for 7 consecutive days. The mice were weighed before the experiment, on the 7th and 14th days. On the 13th day, the elevated cross maze test was performed on the mice. The open field test was performed on the 14th day. After the experiment, immunofluorescence assay was used to determine the expression of microglial ionized calcium binding adaptor molecule-1(Iba-1) in prefrontal cortex region. The mRNA expression of NF-κB, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), Caspase-1 and interleukin (IL)-18 were detected by Real-time PCR. The protein expression levels of NF-κB, iNOS, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, IL-1β and IL-18 were detected by Western blotting.  Results   Weight change, On the 7th day, compared with the control group, the body weight of mice in model group, sham electroacupuncture group and electroacupuncture group decreased (P<0.0001), respectively; On the 14th day, compared with the control group, the weight of mice in the model group decreased (P<0.0001); Compared with the sham electroacupuncture group, the body weight of mice in the electroacupuncture group increased (P<0.05). Elevated cross maze experiment, compared with the control group, the total distance and open arm retention time of mice in model group decreased, while the closed arm retention time increased (P<0.05). The open field experiment showed that compared with the control group, the model group mice showed a decrease in total distance traveled, slower movement speed, and fewer entries into the central area(P<0.001); Compared with the model group, the electroacupuncture group showed an increase in all three indicators(P<0.01); Compared with the sham electroacupuncture group, the total distance and motion speed of mice in electroacupuncture group both increased (P<0.05). Immunofluorescence assay, compared with the control group, the relative fluorescence of Iba-1 in prefrontal cortex area of mice in model group increased (P<0.05). Compared with the model and sham electroacupuncture group, the relative fluorescence of Iba-1 in prefrontal cortex area of mice in electroacupuncture group decreased (P<0.05). Real-time PCR showed that compared with the control group, mRNA expressions of NF-κB, iNOS, TNF-α, Caspase-1 and IL-18 in the model group increased (P<0.05); Compared with the model group, mRNA expressions of NF-κB, iNOS, TNF-α, Caspase-1 and IL-18 in electroacupuncture group decreased (P<0.05). Western blotting indicated that compared with the control group, the protein expressions of NF-κB, iNOS, Caspase-1, IL-1β and IL-18 in model group increased (P<0.05); Compared with model group, the protein expressions of NF-κB, iNOS, NLRP3, ASC, Caspase-1, IL-1β and IL-18 in electroacupuncture group decreased (P<0.05); Compared with the sham electroacupuncture group, IL-18 protein in electroacupuncture group decreased (P<0.05).  Conclusion   Electroacupuncture can improve the behavioral performance of mice and inhibit the activation of microglia in the cortical region of mice, which may play an anti-inflammatory and protective role by regulating NF-κB/ NLRP3 pathway. 

Objective To investigate the antitumor effects of triptolide against CT26 colon cancer and its impact on the expression of Polo-like kinase-1 (PLK-1) protein.  Methods  Forty clean grade BALB/c mice, each mouse was implanted with 1×10⁶ CT26 cells into the dorsal side of the right forelimb to establish a tumor-bearing mouse model. Experimental animals were randomly divided into four groups, the tumor model group (saline control), the positive drug group ［oxaliplatin, 5mg/(kg·d)］, the low-dose triptolide group ［50μg/(kg·/d)］, and the high-dose triptolide group ［100μg/(kg·d)］. The drugs were administered through intraperitoneal injection (10 times in total, once every other day). The in vitro effects of the drugs on the proliferation, migration, invasion, and mitosis of CT26 cells were also assessed.   Results  Triptolide significantly inhibited the proliferation, migration, and invasion of CT26 colon cancer cells, and disrupted the separation of centrosomes and the correct arrangement of chromosomes during the prophase of mitosis in tumor cells. The binding energy of triptolide and PLK-1 protein was -7.1 kcal/mol, and it could down-regulate the expression of PLK-1 in CT26 cells.  Conclusion  Triptolide exerts its antitumor effects against CT26 colon cancer by downregulating the expression of PLK-1.

Objective  To survey and analysis of cephalometric indicators of Wa adults in China.  Methods  Cephalometric parameters were measured in 1996 cases (858 males and 1138 females) of Wa adults in China, including 927 cases (381 males and 546 females) of the Baraoke ethnic group, 564 cases (241 males and 323 females)of the A Wa ethnic group, and 505 cases (236 males and 269 females) of the Wa ethnic group by using sliding caliper and spreading caliper. Seventeen direct cephalofacial parameters and one indirect parameter for each of the three dialect ethnic groups were derived separately and analyzed for age correlations, inter-sex u-tests,and multiple comparisons. Finally, the three dialect ethnic groups were subjected to cluster analysis and principal component analysis with 15 ethnic groups in China.  Results   Nose breadth, mouth breadth and physiognomic ear length were significantly and positively correlated with age for both sexes in the three Wa dialect ethnic groups, while head breadth and lip height were significantly and negatively correlated with age. Except for the interocular breadth, there were gender differences between males and females in the cephalometric parameters of the three Wa dialect ethnic groups. The cephalofacial features of the Baraoke, A Wa and Wa ethnic groups were different, as evidenced by the fact that males and females of the Baraoke and Wa dialect ethnic group had higher lip height, wider nasal breadth and wider mouth breadth, while males and females of the A Wa ethnic group had lower nasal height.  Conclusion   The cephalofacial features of the three Wa dialect ethnic groups are close to those of the Khmus and Mang, who have their origins in the ancient Baipu people and are also members of the Mon-Khmer language group of the Austroasiatic linguistic. 

There are a variety of mechanical signals in the microenvironment of cells, which have temporal and spatial variability, which jointly regulate the histological processes such as cell proliferation, differentiation and migration. Piezo1 is a mechanically sensitive cationic channel. As a force sensor, it transmits signals to downstream pathways and participates in a variety of life activities in response to changes in the cell microenvironment. In this paper, the common signal pathways of Piezo1 were reviewed in order to identify the downstream signaling pathways regulated by Piezo1, thereby providing theoretical basis for inhibiting or delaying related diseases.

Objective  To investigate the effect of nobiletin on plateletactivating factor (PAF) metabolism in diabetic rats with renal injury.  Methods   Totally 72 rats were randomly divided into control group (n=10) and modeling group (n=62). The modeling group rats were induced to develop a diabetic rat model with renal injury and then further divided into the model group, aspirin group (20mg/kg), and nobiletin low(50mg/kg), medium(100mg/kg), and high-dose (200mg/kg) groups, each with 10 rats. After continuous oral administration for 6 weeks, rat body weight, kidney weight, and kidney index were measured. Histopathological assessments were conducted by using HE, periodic acid-Schiff staining (PAS), Masson staining, and transmission electron microscopy. Blood glucose levels, renal function, inflammatory factors, PAF and its regulatory factors were detected. Expression levels of PAF metabolism-related proteins, PAF-acetylhydrolase(PAFAH), PAF receptor (PAFR), and cholinephosphotransferase 1(CHPT1) in kidney tissues were assessed using Western blotting and immunohistochemistry.  Results   Following nobiletin intervention, rat body weight increased while kidney weight and kidney index decreased. Improvement in renal tissue pathology was observed, with reduced interstitial fibrosis and thinner basement membrane. Fasting blood glucose and glycated hemoglobin decreased, while fasting insulin showed no significant improvement. Urea nitrogen, blood creatinine, cystatin C, and 24-hour urinary protein excretion were reduced. Levels of interleukin (IL)-1α, IL-6, IL-8, and tumor necrosis factor (TNF-α) were lowered. PAF and its regulatory factors decreased. PAFR and CHPT1 expression decreased, while PAFAH increased.  Conclusion   Nobiletin can alleviate renal injury in diabetic rats with renal injury, improve kidney function, regulate blood glucose, and mitigate inflammatory response. Its mechanism may be associated with the modulation of platelet-activating factor metabolism. 

Objective  To investigate the formation and mechanism of dipeptidylpeptidase-4 inhibitor anagliptin inhibiting lung metastasis of colorectal cancer.  Methods   Twenty-four male BALB/c mice were randomly divided into normal group, model group, anagliptin group. The control group did not undergo any treatment. The model group was injected with 0.1 ml CT-26 cells of 109 cells/L. once through the tail vein of the mouse to construct a lung metastasis model, while the anagliptin group was injected intraperitoneally 20mg/(kg·d) 0 day after  constructing a lung metastasis model. The mice were sacrificed after 14 days. HE staining was used to detect the morphological alteration. Determination of CT-26 cell viability through MTT assay and CT-26 cell apoptosis was detected by flow cytometry and live/dead cell staining. Reactive oxygen species(ROS) production was measured by ROS kit. Western blotting was conducted to measure the expression level of Bcl-2, Bax, cleaved-caspase-3, superoxide dismutase(SOD-1) and SOD-2.  Results   HE staining showed that the administration of anagliptin could significantly inhibit the abnormal changes in the model group. Anagliptin inhibited the viability of CT-26 cells above 2 mmol/L. Anagliptin promoted the apoptosis of CT-26 cells. Incubation of anagliptin in CT-26 cells significant promoted the production of ROS. Incubation of anagliptin stimulated the expressions of Bax and cleaved-Caspase-3, while down-regulated the expression of Bcl-2 in CT-26 cells. Administration of anagliptin decreased the expression of SOD-1, but not SOD-2.  Conclusion   Anagliptin promotes apoptosis of colorectal cancer cells and inhibits the formation of lung metastatic tumors through the SOD-1/ROS pathway.  

Objective To explore the mechanism of action of jolkinolide B in the treatment of gastric cancer by network pharmacology combined with molecular docking technique.   Methods The SwissTargetPrediction database was used to obtain the targets of the active compounds. Search Genecards, OMIM, Drugbank, TTD, and PharmGKB databases to obtain targets for gastric cancer. The intersection between the targets of jolkinolide B and those of gastric cancer was identified pinpoint potential targets for jolkinolide B in treating gastric cancer. The String database was utilized construct a protein-protein interaction(PPI) network. Bioconductor bioinformatics packages with R software was employed conduct Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the shared targets. This process revealed significant regulatory pathways crucial for jolkinolide B’s efficacy in treating gastric cancer. Cytoscape 3.7.1 software was utilized create the core network of “Potential Targets of Triptolide B in Gastric Cancer Treatment”, and SYBYL-X2.1.1 software was employed conduct molecular docking validation of the selected main active ingredients and critical targets.   Results Jolkinolide B may target multiple proteins, including MAPK1, glycogen synthase kinae-3β(GSK-3β), and JUN, impacting the proliferation, invasion, and metastasis of gastric cancer, ultimately inhibiting its growth.     ConclusionWe predicted the possible molecular mechanism of jolkinolide B in the treatment of gastric cancer to provide guide information for the subsequent experimental research and clinical application.

Objective   To investigate the effects of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in coronary arteriosclerosis (AS) on the migration of stem cell antigen-1(Scal-1) and Nanog positive cells migration.  Methods   Ten atherosclerotic model mice and 10 normal mice were taken respectively, and the fresh hearts of the two groups were taken out, OCT embedding, frozen sections, HE staining and oil red O staining were performed respectively to observe the pathological changes of coronary arteries; Using immunohistochemical staining techniques, the expression changes of TNF-α, IL-6, Scal-1, and Nanog in the coronary artery wall were observed under light microscope. The ventricular tissue of 20 1-week-old mice was excised. Primary Scal-1 and Nanog positive cells were extracted using density gradient centrifugation, and these cells were purified and cultured. Immunofluorescence technology was used to identify the purity of Scal-1 and Nanog positive cells. Transwell migration experiments on passage 1(P1) cells was performed to observe the effects of different concentrations of inflammatory factors on the migration of Scal-1 and Nanog positive cells.  Results  The blood lipid test showed that the total cholesterol, triglycerides, and low-density lipoprotein cholesterol of the model mice were significantly higher than those of the normal control group. Histological staining showed that all the mouse models had obvious coronary atherosclerosis plaque. Immunohistochemical staining results showed that the inflammatory factor TNF-α and IL-6 in atherosclerosis region were strong positive expression, while Scal-1 and Nanog positive cells in atherosclerotic plaques increased, compared to the normal group. The positive rate of Scal-1 in P1 generation cells was about 80%, The positive rate of Nanog was approximately 91%. The Transwell experiment showed that IL-6 had no effect on cell migration at low concentrations, but had an inhibitory effect on cell migration at high concentrations; Low concentrations TNF-α promoted cell migration with 0.5 μg/L TNF-α showing the most significant effection cell migration, and exhibiting inhibitcry effects inhibit at high concentrations.  Conclusion   TNF-α  and IL-6 inflammatory factors, Scal-1 and Nanog positive cells are all involved in the occurrence and development of AS, and the appropriate concentration of inflammatory factors can enhance the migration of stem cells to the coronary atherosclerosis region. 

Objective To investigate the differentiation of oligodendrocyte precursor cells after neural injury utilizing Sox10 cell lineage tracing in the cortical tissue. Methods  C57BL/6 mice and Sox10-CreERT2/red fluorescent protein(RFP) model mice were used in the current study. The Sox10-CreERT2/RFP model mice generated by crossing Sox10-CreERT2 and Ai9 were 8-week-old F1 mice (n =16), which were randomly divided into control group (n =4) and 7 days (n =4), 14 days (n =4), and 30 days feed groups (n =4). Tamoxifen(TAM) was used to induce the expression of RFP. The control group received tamoxifen dissolved in sunflower seed oil by gavage (40 mg/kg once daily for three consecutive days) and the brain tissues were obtained after 4 days. The feed group mice were fed with tamoxifen-containing feed to induce RFP expression, and the brain tissues were obtained after 7, 14, and 30 days, respectively. Immunofluorescent staining was performed to detect the expressions of neuronal nuclei (NeuN), microtubuleassociated protein 2 (MAP2), phosphorylated histone 2AX (γ-H2AX), cluster of differentiation 13 (CD13), γaminobutyric acid (GABA), glial fibrillary acidic protein (GFAP), cluster of differentiation 11b (CD11b), vesicular glutamate transporter 2 (VGLUT2), and adenomatous polyposis coli (APC, CC-1) in the brains of each group mice. The number of positive cells was counted, and the proportion was calculated. Eight-week-old male C57BL/6 mice were randomly divided into wild type(WT) group (n =4) and WT+TAM group (n =4). They were fed with regular feed and tamoxifencontaining feed for 30 days, respectively, and then brain tissues were obtained. Immunofluorescent double-labeling was used to detect the expressions of γ-H2AX positive neurons in the cortex of mice in both groups.   Results  In the control group, feed 7 days,14 days, and 30 days groups, the proportions of RFP⁺ pericytes among all RFP⁺ cells in the cortical tissue were (0.8±0.1)%, (2.7±0.1)%, (3.2±0.1)%, (4.0 ±0.1)%, respectively, and the proportion of mature oligodendrocytes (CC-1⁺ RFP⁺) in the feed 7 days group was (51.2±0.7)%. The proportions of RFPpositive neurons in the cortex after 14 and 30 days of tamoxifen feed were (0.7±0.1)% and (1.5±0.1)%, respectively, while no conversion to RFP-positive neurons was observed in the gavage group and 7 days feed group. RFP cells in the cortex of the 7 days or 30 days feed group did not express GFAP or CD11b. Extensive γ-H2AX⁺ NeuN⁺ staining was observed in the WT group and WT+TAM group. Conclusion  Long-term administration of tamoxifen can promote the differentiation of Sox10 cells into pericytes and neurons. Further investigation into the role of OPC in the neurovascular unit repair mechanism may contribute to a better understanding of the pathogenesis underlying AD. 

Objective  To measure the distal space between skeletal class Ⅲ and skeletal class Ⅰ mandibular molars, compare the differences, and to measure the contact situation between the distal root tip of the second mandibular molar and the lingual cortical bone of the mandible, providing a theoretical reference for the distance of mandibular molar distal movement by using cone beam CT(CBCT).  Methods   CBCT imaging data of 60 adult patients who received orthodontic treatment at Chengde Stomatological Hospital from 2020 to 2022 were selected, including 30 patients with skeletal class Ⅲ mean angle and 30 patients with skeletal class Ⅰ mean angle. CBCT image data were exported to DICOM format, then import it into Mimics 20.0 software, and measure the distal space of bilateral mandibular second molars. The contact between the distal root tip of the second mandibular molar and the lingual bone cortex of the mandible was measured. Import the measurement results into SPSS 19.0 statistical software to analyze the differences and the contact rate.  Results   There was no statistical difference in the measurement results of the distal space of mandibular molars between genders, and sides, and between mandibular molars with or without wisdom teeth (P>0.05). The distal space of mandibular molars in skeletal class Ⅲ were greater than those in skeletal class I, and the difference was statistically significant (P<0.05). The contact rate between the distal root tip of the second mandibular molar and the lingual bone cortex of the mandible was 34.83%. There was no significant difference in the contact rate between the distal root tip of the mandibular second molars and the lingual cortical bone of the mandible between class Ⅲ malocclusion and class I malocclusion(P>0.05).  Conclusion   There is a certain gap in the distal part of the skeletal class Ⅲ mandibular molar. In clinical practice, the molar can be designed to move distally, expanding the dental arch from the sagittal direction to provide a gap for the adduction of the mandibular anterior teeth. However, it is necessary to evaluate the contact between the distal root tip of the second mandibular molar and the lingual bone cortex of the mandible. If the distal root tip of the second mandibular molar contacts the lingual bone cortex of the mandible, the distal movement of the molars should be avoided. 

Objective  To investigate the spatiotemporal variations in sexual size dimorphism among Chinese Han students.  Methods  Based on the eight students’physical and healthy investigations, the data on the stature and body mass were systematically collected for 343 928 and 344 029 Chinese Han students aged 19 to 22 years from 1985 to 2019, respectively. The sexual stature dimorphism index (SSDI) and sexual body mass dimorphism index (SBMDI) were employed to analyze the distribution in different periods and regions. In addition, we focused the relationships between these two indices and the per capita consumption expenditure. Results  Positive secular trends were observed in the SSDI and SBWDI among Chinese Han students throughout the 1985 to 2019 period. Notable similarities were identified in the SSDI and SBWDI between northern and southern students. Compared with the SSDI, the SBWDI exhibited significant disparities between urban and rural areas, and demonstrated a positive association with the per capita consumption expenditure.  Conclusion  The female buffering hypothesis possesses a limited range of spatiotemporal adaptability, and the trait more susceptible to environmental influences is better suited to test this hypothesis. 

Objective  To explore the effect of gastrodin（GAS）on the polarization of M2 microglia under oxygen and glucose deprivation（OGD）and the effect of p38 MAPK inhibition on the polarization status of microglia.  Methods BV2 microglia was divided into the control group（Ctrl），p38 MAPK inhibitor SB203580 group（I），OGD group (OGD)，OGD+I group，gastrodin treatment group（G+OGD），and G+OGD+I group. The expressions of p38 MAPK，phosphorylated p38 MAPK（p-p38 MAPK）, M2 microglia marker arginase-1 (Arg-1) and chitinase like protein 1/2（YM1/2）were detected by immunofluorescent staining and Western blotting. Results  Immunofluorescent staining results showed that the pretreatment with gastrodin reduced the fluorescence expression of p-p38 MAPK in OGD induced BV2 microglia, enhanced the fluorescence expressions of Arg-1 and YM1/2. After pretreatment with SB203580，the fluorescence expressions of p-p38 MAPK further decreased，the fluorescence expressions of Arg1 and YM1/2 further increased，both were significantly different from the G+OGD group （ n=3，P<0.05）. The fluorescence expressions of p38 MAPK in each group was not statistically significant（ n=3，P>0.05）. Western blotting results showed that the protein expressions of p-p38 MAPK, Arg-1 and YM1/2 in the OGD group enhanced，compared with that in the control group（ n=3，P<0.05）. After the pretreatment with gastrodin，the protein expression of p-p38 MAPK was reduced significantly，the protein expressions of Arg-1 and YM1/2 was enhanced obviously，both were significantly different from the OGD group （ n=3，P<0.05）. After pretreatment with SB203580，the protein expressions of p-p38 MAPK was further reduced，the protein expression of Arg-1 and YM1/2 were further enhanced，both were significantly different from the G+OGD group（ n=3，P<0.05）. In addition，there was no significant change in p38 MAPK protein expression among groups （ n=3，P>0.05）.  Conclusion  Gastrodin inhibits p38 MAPK signaling activation to promote BV2 microglial polarization towards the M2 phenotype，reducing inflammatory responses and exerting a protective effect. 

Objective To investigate the related mechanism which metformin inhibited the proliferation of HCT116 colorectal cancer cells via down-regulating the expression of up-frameshift protein 1 (UPF1).     Methods TCGA and UALCAN databases were utilized to analyze the expression level of UPF1, while Western blotting and Real-time PCR were performed to validate the differences of UPF1 expressions in colon cancer tissues and adjacent normal tissues. Clone formation assay, CCK-8 assay, wound healing assay and Transwell invasion assay were used to examine the effects of knockdown UPF1 on the proliferation, migration and invasion of HCT116 cells respectively. The HCT116 cell dataset with UPF1 knockdown was screened from GEO database for Kyoto Encydopedia of Genes and Genomes(KEGG) pathway analysis, the expression level of differential genes that enriched in Hippo pathway were verified by Real-time PCR. The HCT116 cells were treated with metformin, Western blotting and Real-time PCR were employed to detect the UPF1 expression. Mendelian randomization analysis was performed to explore the causal association between metformin treatment and colorectal cancer.     Results Analysis of TCGA and UALCAN databases showed that both UPF1 mRNA and protein were highly expressed in colon cancer tissues and the expression level of UPF1 was closely correlated with clinicopathologic stage and lymph node metastasis. Compared with adjacent normal tissues, the UPF1 protein and mRNA were highly expressed in colon cancer tissues. Knockdown UPF1 expression could inhibit the proliferation, migration and invasive ability of HCT116 cells. There were 8 differential genes affect the Hippo pathway by KEGG enrichment analysis, Real-time PCR experiments confirmed that CTNNB1, BMP4, TEAD2, PARD6G and FZD1 mRNA decreased in HCT116 cells with UPF1 knockdown. Both UPF1 protein and mRNA expressions decreased after metformin treatment in HCT116 cells. Mendelian randomization analysis showed a negative causal association between metformin treatment and colorectal cancer.      Conclusion Knockdown of UPF1 expression inhibits the proliferation of HCT116 cells through regulating Hippo pathway. Metformin can reduce the UPF1 expression for further inhibiting the proliferation of colorectal cancer cells.

Objective To develop a melanoma diagnosis framework based on large-scale vision-language models, and to explore the feasibility and accuracy of the framework for melanoma diagnosis.   Methods The publicly available Derm7pt dataset, which was divided into a training set (346 cases), a validation set (161 cases), and a test set (320 cases) was utilized. A melanoma diagnosis framework based on large-scale vision-language models was proposed, comprising two text branches and one visual branch. In the text branches, one branch processed fixed clinical prompts, while the other handled learnable prompts. This design aimed to optimize the effectiveness of learnable prompts through guidance from fixed clinical prompts. The visual branch processed dermoscopic images and enhanced melanoma feature recognition through fine-tuning the image encoder.   Results On the Derm7pt dataset, our method  outperformd other existing method. It achieved an area under the receiver operating characteristic curve (AUC) of 87.35%, an accuracy of 84.17%, and an F1-score of 84.01%.   Conclusion The study demonstrates that with appropriate fine-tuning strategies, methods based on large-scale vision-language pre-trained models can effectively adapt to melanoma diagnosis tasks. This approach can serve as a powerful auxiliary tool for doctors, helping them make more accurate diagnostic decisions.

Objective To observe the difference of bone micro-structure in different regions of proximal femur, micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.     Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers. Micro-CT scanning was used to measure the trabecular thickness(Tb.Th), trabecular number(Tb.N), trabecular space(Tb.Sp), connectivity(Conn) and bone mineral density(BMD) and other parameters in 7 regions of proximal femur, including proximal pressure trabecular(PPT), distal pressure trabecular(DPT), femoral head-neck junction(FHNJ), head and neck of femoral neck(HNFN), the base of femoral neck(BPFN), intertrochanteric line(IL) and greater trochanter(GT).    Results The bone mineral density of IL and GT were higher than those of BPFN, FHNJ, DPT and PPT. The trabecular thickness of GT was the largest, followed by IL, BPFN and HNFN, and the smallest was FHNJ, DPT and PPT. The trabecular space of IL was larger than that of GT, and the data of both were larger than those of other parts, among which DPT and PPT were the smallest. The trabecular number of IL and GT were the smallest, BPFN, HNFN and FHNJ were larger, and DPT was the largest. The volume fraction of IL was the smallest, BPFN and HNFN were larger, DPT and PPT were the largest.     Conclusion The bone density, trabecular thickness, bone volume, and total volume of GT and IL in the proximal femur of elderly patients are all relatively large, so the reason for the high incidence of fractures is not due to weak internal bone microstructure; The bone density, trabecular thickness, and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small. If it is necessary to perform core decompression for prosthesis filling at this location, the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.